Bacterial vaginosis (BV) is the most prevalent cause of symptomatic vaginal discharge in the U.S. and has been associated with complications including preterm delivery of infants, pelvic inflammatory disease (PID), urinary tract infections and acquisition/transmission of sexually transmitted diseases (STDs) including HIV. Control of BV has been advocated for decreasing the prevalence of these complications, however, the etiology of BV remains unknown and current treatment regimens are inadequate. Although the pathogenesis of BV is poorly understood, it does appear that the changes leading to BV may be progressive. Vaginal Gram stains are able to detect an intermediate flora pattern which has been shown to either revert back to normal or progress to BV. Progression to BV has been shown to occur in one-third of these women (1). In recent years renewed attention has been paid to potential importance of GV as a founder organism necessary for the initiation of the events which lead to BV. It is possible that specific strains or clades of GV are more virulent, either by possession of virulence factors which enhance infectious capability of the host and/or possess toxigenic capabilities to directly suppress colonization by the normal vaginal flora, and thus are more likely to be important in the pathogenesis of BV and its complications. These differences in virulence may also be applicable to the pathogenesis of chlamydial infections and NGU (see Projects 1 and 3). In this project we plan to examine specific virulence factors of GV and correlate their presence with progression to BV (Project 2) as well as pathogenesis of NGU (Project 1) and pathogenesis and transmission of chlamydial infections (Project 3). Additionally, we will examine a classification system for GV based on enzymatic and genetic characteristics. This type of classification could potentially lead to refined diagnosis and management of abnormal vaginal flora. To accomplish these goals we will conduct a prospective, longitudinal study of women with GV but no evidence of BV to determine if there is strain differences associated with the development of the BV syndrome.